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Poster session 06

1665P - Genomic mutational landscape of solid tumors: Preliminary results from ROME trial

Date

10 Sep 2022

Session

Poster session 06

Topics

Cancer Biology;  Tumour Immunology;  Pathology/Molecular Biology;  Translational Research;  Molecular Oncology

Tumour Site

Presenters

Andrea Botticelli

Citation

Annals of Oncology (2022) 33 (suppl_7): S758-S771. 10.1016/annonc/annonc1078

Authors

A. Botticelli1, S. Scagnoli2, P.F. Conte3, C. Cremolini4, P.A. Ascierto5, F. Cappuzzo6, M. Aglietta7, F. Mazzuca8, E. Capoluongo9, G. Blandino10, U. Malapelle11, M. Nuti12, G. D'Amati1, B. Cerbelli1, G. Pruneri13, M. Biffoni14, G. Giannini15, F. Cognetti16, G. Curigliano17, P. Marchetti18

Author affiliations

  • 1 C Department Of Radiology, Oncology And Human Pathology, Sapienza University of Rome, 00161 - Rome/IT
  • 2 B Department Of Medical And Surgical Sciences And Translational Medicine, Sapienza University of Rome, 00189 - Rome/IT
  • 3 Surgery, Oncology And Gastroenterology Department, IOV - Istituto Oncologico Veneto IRCCS, 35128 - Padova/IT
  • 4 Unit Of Medical Oncology And Department Of Translational Research And New Technologies In Medicine, University of Pisa, 56126 - Pisa/IT
  • 5 Melanoma, Cancer Immunotherapy & Developmental Therapeutics, Istituto Nazionale Tumori - IRCCS - Fondazione Pascale, 80131 - Napoli/IT
  • 6 Medical Oncology 2, IRCCS Istiuto Nazionale Tumori Regina Elena (IRE), 00144 - Rome/IT
  • 7 Medical Oncology Department, IRCCS - Istituto di Candiolo - FPO, 10060 - Candiolo/IT
  • 8 Department Of Clinical And Molecular Medicine, AOU Sant'Andrea - Università Sapienza di Roma, 00189 - Rome/IT
  • 9 Department Of Molecular Medicine And Medical Biotecnology, Università degli Studi di Napoli Federico II, 80138 - Napoli/IT
  • 10 Laboratorio Di Oncogenomica Ed Epigenetica, IRCCS Istiuto Nazionale Tumori Regina Elena (IRE), 00144 - Rome/IT
  • 11 Public Health Dept., Università degli Studi di Napoli Federico II - Scuola di Medicina e Chirurgia, 80131 - Napoli/IT
  • 12 Experimental Medicine Dept., Sapienza University of Rome, 00161 - Rome/IT
  • 13 Department Of Pathology, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 14 Oncology And Molecular Medicine Department, Istituto Superiore di Sanità (ISS), 161 - Rome/IT
  • 15 Department Of Molecular Medicine, Sapienza - Università di Roma, 00161 - Rome/IT
  • 16 Medical Oncology Dept., IRCCS Istiuto Nazionale Tumori Regina Elena (IRE), 00144 - Rome/IT
  • 17 Early Drug Development For Innovative Therapies Division, IRCCS European Institute of Oncology - University of Milano, 20141 - Milan/IT
  • 18 Oncologia E Oncologia Dermatologica, IRCCS Istituto Dermopatologico dell'Immacolata IDI, 00189 - Rome/IT
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Abstract 1665P

Background

The Rome trial is a randomized phase II trial (NCT04591431). The aim is to evaluate the feasibility on large scale and the clinical utility of a tailored treatment (TT) in patients (pts) compared to standard of care (SoC) with solid tumors. Here we report the preliminary results of the molecular alterations detected during the screening phase.

Methods

Centralized NGS was performed on both tumor tissue, collected within 6 months, and liquid biopsy from pts with refractory malignancies. Molecular alterations were evaluated by Molecular Tumor Board (MTB) using COSMIC, ClinVar, OncoKB and VarSome datasets. All pts with actionable genomic alterations were weekly discussed by the MTB. Genes with at least 10% frequency of mutation, microsatellite status (MS) and tumor mutational burden (TMB) were collected.

Results

From Oct 2020 to Apr 2022, 792 pts were enrolled from 40 italian hospitals. To date, we have complete mutational data of 482 patients. Molecular profiling was available both on tissue and liquid biopsy in 414 (86%) pts, while 13 and 53 had only tissue or liquid test available. 3138 genomic alterations were identified in 258 genes with a median of 7.9 alterations (0-35). The most frequent altered genes were: TP53 (57%), PIK3CA (21%), KRAS (28%), DNMT3A (22%), CDKN2A (19%), APC (16%), PTEN (12%), ARID1A (12%), ERBB2 (11%), NRAS (11%), ATM (10%), TET2 (11%). The most frequent altered pathways were TP53 (57%), RAS/RAF (47%), Cell cycle/cycline (38%), PI3KCA/AKT/MTOR (28%), Homologous Recombination system (20%). The most common actionable alterations with TT available in the ROME trial were: PIK3CA/AKT (24%), H-TMB/MSI (17%), FGFR1/2/3 (9%), EGFR (9%), BRAF V600/nonV600 (6%), JAK 1/2/3 (3%), NTRK1-3/ROS1 (2%), RET (2%), PTCH1 (1.5%), ALK (1%).17 pts were MSI (3.5%). Overall median TMB was 9.7 (0-458) while median TMB for MSS and MSI pts were 5.9 (0-35) and 96.0 (24-458), respectively. MSS pts with a TMB >10 mut/mb were 65 (13.5%). Actionable mutations were detected in 202 pts (43%) and 130 (27%) were randomized in the trial after the MTB discussion.

Conclusions

ROME trial demonstrates the feasibility of extensive molecular profiling and discussion in MTB. Almost 30% of pts had molecular alterations for which a target strategy was available in the trial.

Clinical trial identification

MAR-BAS-18-005; EudraCT n° 2018-002190-21; NCT04591431.

Editorial acknowledgement

Legal entity responsible for the study

Fondazione per la Medicina Personalizzata (FMP).

Funding

Roche, Novartis, Pfizer, BMS, Incyte, Takeda.

Disclosure

A. Botticelli: Financial Interests, Institutional, Speaker’s Bureau: Roche, MSD, Novartis, Pfizer, Lilly, Amgen, BMS; Financial Interests, Institutional, Advisory Board: Roche, MSD, Lilly, BMS; Non-Financial Interests, Institutional, Advisory Board: Novartis, Pfizer, Amgen. S. Scagnoli: Financial Interests, Institutional, Invited Speaker: Lilly, Pfizer; Financial Interests, Institutional, Speaker’s Bureau: Lilly, Novartis, MSD, Roche; Financial Interests, Institutional, Advisory Board: Novartis. P.F. Conte: Financial Interests, Institutional, Advisory Board: Daiichi Sankyo, Lilly, reveal genomics; Non-Financial Interests, Institutional, Advisory Board: Gilead; Financial Interests, Institutional, Speaker’s Bureau: Roche, Genentech, Novartis, AstraZeneca, Lilly, Tesaro, BMS; Financial Interests, Institutional, Funding: Roche, Novartis, Merck-Serono, BMS; Financial Interests, Personal, Ownership Interest: HER2dx patent; Financial Interests, Institutional, Expert Testimony: Roche, AstraZeneca. C. Cremolini: Financial Interests, Personal, Advisory Board: Roche, MSD; Financial Interests, Personal, Invited Speaker: Bayer, Servier; Financial Interests, Personal, Expert Testimony: Amgen; Financial Interests, Institutional, Invited Speaker: Roche, Bayer, Servier, Merck. P.A. Ascierto: Financial Interests, Personal, Other, Consultant and Advisory Role: BMS, Roche Genentech, MSD, Novartis, Pfizer/Array, Merck Serono, Pierre Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Nektar, Boehringer Ingelheim, Regeneron; Financial Interests, Personal, Other, Consultant Role: Italfarmaco; Financial Interests, Personal, Other, Advisory Role: Eisai, Seagen; Financial Interests, Personal, Other, Consultant Role: Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore; Financial Interests, Personal, Other, Consultant role: Medicenna, Bio-AI Health; Financial Interests, Personal, Advisory Board, Consultant and Advisory Role: Dohme, iTeos; Financial Interests, Institutional, Funding, Clinical trial and translational research: BMS; Financial Interests, Institutional, Funding, Clinical Trial: Roche Genentech, Pfizer/Array, Sanofi; Non-Financial Interests, Leadership Role, President since 2010: Fondazione Melanoma Onlus Italy; Non-Financial Interests, Leadership Role, President since 2014: Campania Society of ImmunoTherapy of Cancer (SCITO) Italy; Non-Financial Interests, Other, Member of Steering Committee since 2016: Society for Melanoma Research (SMR); Non-Financial Interests, Invited Speaker, November 2017 - December 2021: Society for Immunotherapy of Cancer (SITC); Non-Financial Interests, Member: ASCO, SITC, EORTC Melanoma Cooperative Group, AIOM, SMR; Other, Travel Support: MSD. F. Cappuzzo: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, PharmaMar, Mirati, Novocure, OSE, and MSD; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, Mirati, PharmaMar, Novocure, OSE, GALECTO and MSD. M. Aglietta: Financial Interests, Institutional, Advisory Role: BMS; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Affiliate: PharmaMar travel; Financial Interests, Institutional, Speaker’s Bureau: BMS; Financial Interests, Institutional, Invited Speaker: Merk, Tesaro. F. Mazzuca: Financial Interests, Institutional, Speaker’s Bureau: Amgen, Lilly, Bayer, Merk, Novartis; Financial Interests, Institutional, Other, honoraria: Amgen, Lilly, Merk, Novartis; Financial Interests, Institutional, Advisory Board: Bayer. E. Capoluongo: Financial Interests, Institutional, Other, honoraria: MSD, AstraZeneca, GSK; Financial Interests, Institutional, Advisory Board: GSK, AstraZeneca, MSD; Financial Interests, Institutional, Speaker’s Bureau: GSK, AstraZeneca, MSD. U. Malapelle: Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, Roche, MSD, Amgen, Thermo Fisher Scientifics, Eli Lilly, GSK, Merck, AstraZeneca; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Roche, MSD, Amgen, Thermo Fisher Scientifics, Eli Lilly, Diaceutics, GSK, Merck, AstraZeneca, Janssen, Diatech, Novartis, Hedera. M. Nuti: Financial Interests, Institutional, Funding: Incyte, Ipsen. G. D'Amati: Financial Interests, Institutional, Advisory Board: Roche, Merck Sharp & Dohme. B. Cerbelli: Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Training: MSD. G. Pruneri: Non-Financial Interests, Institutional, Other, honoraria: Exact science, foundation one, Novartis, AstraZeneca, Bayer; Non-Financial Interests, Institutional, Advisory Board: Ads Biotec. F. Cognetti: Non-Financial Interests, Institutional, Other, honoraria: GlaxoSmithKline, AstraZeneca; Non-Financial Interests, Institutional, Advisory Role: GlaxoSmithKline, Seagen, Pfizer; Non-Financial Interests, Institutional, Advisory Board: Dompè, Roche, Lilly, Genomic Health; Non-Financial Interests, Institutional, Speaker’s Bureau: Roche, Pfizer, AstraZeneca, Lilly, Pierre Fabre, Genomic Health. G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Ellipsis, Roche, AstraZeneca, Daiichi Sankyo, Lilly, Pfizer, Veracyte, BMS, Merck, Exact Sciences; Financial Interests, Personal, Advisory Board, Advisory Board: Exact Science, Celcuity; Financial Interests, Institutional, Research Grant, Investigator Initiated Trial: Merck; Financial Interests, Institutional, Funding, Phase I studies: BMS, Novartis, AstraZeneca, Daiichi Sankyo, Roche, Blueprint Medicine, Kymab, Astellas, Sanofi, Philogen; Financial Interests, Institutional, Invited Speaker, Phase I clinical basket trial: Relay Therapeutics; Non-Financial Interests, Officer, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Advisory Role, Member of the Scientific Council. Patient advocacy association: Europa Donna; Non-Financial Interests, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Invited Speaker, No compensation for this role. This a public national company for cancer prevention: Lega Italiana Lotta ai Tumori; Non-Financial Interests, Officer, Member of the Advisory Council: EUSOMA. P. Marchetti: Financial Interests, Institutional, Research Grant: Roche, MSD, BMS, AstraZeneca, Boehringer, Novartis, Pfizer; Financial Interests, Institutional, Speaker’s Bureau: Roche, MSD, BMS, Lilly, Novartis, Pfizer; Financial Interests, Institutional, Advisory Board: BMS, Roche, Pfizer, Lilly. All other authors have declared no conflicts of interest.

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